DE112018002960B4 - LIQUID DISPENSING UNIT WITH HYDROPHOBIC SURFACE - Google Patents

Abstract

A liquid dispenser (200) comprising: a first substrate (210) having a container (222) formed in the first substrate; a liquid (230) received in the container (222); one on the surface of the first substrate a disposed membrane (220) covering an opening of the container (222); a second substrate (209) adhered to the first substrate (210), the second substrate having a container seal (206); one on an inner surface of the membrane (220) ) arranged hydrophobic layer (224), wherein the hydrophobic layer (224) forms an air cushion between a surface of the liquid and the membrane (220); electrodes which are in electrical contact with the membrane (220); and a hydrophilic layer (232) disposed on a surface of the container (222) opposite the membrane (220).

Description

BACKGROUND OF THE INVENTION

The present invention relates generally to miniaturized dispensing units and related methods, and more particularly to liquid dispensing units having hydrophobic surfaces and related methods.

Micrometer scale output units can be useful for a variety of applications. Such dispensing units may include an array of micrometer-sized containers filled with small amounts of a material such as liquids or powders. The containers are sealed with respect to the material and can release the material, for example by tearing or melting a metal membrane. Such micrometer-scale dispensing units can provide for the independent and controlled release of materials in individual containers and can be useful, for example, in drug dispensing applications.

The US 2004/0 020 173 A1 discloses a method of assembling a medicine delivery system which comprises providing a substrate having a plurality of areas, filling the areas with medicine, covering the areas with a cap, heating the system to a relatively low temperature, applying a bias voltage across the Substrate and the cap and applying focused energy to the substrate and / or the cap to seal them together and create a vacuum in the areas. The US 2012/0 305 400 A1 discloses a monolithic manufacturing process of parallel-plate electrowetting-on-dielectric (EWOD) chips for digital microfluidics of picolitre droplets, wherein instead of using a second substrate to form a cover plate, the cover plate is created in situ as a thin film membrane, which forms a monolithic cavity with a gap height on the order of micrometers with excellent accuracy and uniformity. Here reveals the US 2012/0 305 400 A1 that the membrane is embedded in the EWOD drive electrodes and confines the droplets against the device substrate to perform digital microfluidic operations. The US 2016/0 074 323 A1 discloses electromechanical substance delivery devices that implement electromechanical release mechanisms with low power consumption for the controlled delivery of substances such as drugs and medicaments. The US 2016/0 074 323 A1 discloses for an electromechanical device a substrate having a cavity formed in a surface of the substrate, a membrane arranged on the surface of the substrate, which covers an opening of the cavity, and a seal arranged between the membrane and the surface of the substrate, the seal being the Opening of the cavity surrounds, and the seal and the membrane are configured to enclose the cavity and retain a substance in the cavity. The US 2010/0 004 583 A1 discloses an electrotransport drug delivery device that uses a hydrophobic modifier to prevent moisture condensation, the use of a hydrophobic modifier to increase the hydrophobicity of coated parts of the device, a method of reducing moisture condensation on an electrical device, and a method of preserving an electrical device for an electrotransport drug delivery device. The US 2002/0 107 470 A1 discloses methods of manufacturing microchip devices for the controlled release of molecules, such as. B. Medicines, a method of making the devices comprising the steps of: (1) filling a mold with a polymer powder; (2) compressing the powder to form a polymer preform; (3) thermally compression molding the preform to form a substrate in a mold having a plurality of protrusions that form reservoirs in the substrate; and (4) filling the reservoir with a delivery system containing the molecules to be released. Furthermore, the US 2005/0 050 859 A1 A method of hermetically sealing an opening in a reservoir of a containment device, the method comprising applying a polymeric material to an opening in a reservoir of a containment device, the reservoir comprising reservoir contents (such as a drug or a sensor) that are contained within the Reservoirs are to be hermetically isolated, the applied polymeric material closing the opening and forming a temporary seal; and adhering a hermetic sealing material to the polymeric material to hermetically seal the opening.

In some applications, strict specifications for energy storage and power supply may be necessary in order to achieve the desired size of the output unit on the micrometer scale. For example, smaller dimensions of implantable and portable drug dispensing units may be preferred for patient convenience and privacy. However, energy is required to release the material from the container and, in addition, much energy can be lost through conduction within the unit structure. Containers containing liquids can, for example, be affected by undesirably high heat conduction. Thus, there is a need to minimize the energy required to release it from the container.

SHORT REPRESENTATION

The present invention is described by independent claim 1. Further embodiments of the invention are presented in the dependent claims.

Embodiments of the present invention relate to a liquid dispensing device. The device includes a first substrate that includes a container formed in the first substrate. The device also includes a membrane disposed on the surface of the first substrate that covers an opening of the container. According to some embodiments of the invention, the membrane can be a metal layer, an electrically insulating dielectric layer, or a combination of metallic and insulating structures. The device also includes a second substrate adhered to the first substrate, the second substrate including a container seal. The device also includes a hydrophobic layer applied to an inner surface of the membrane. The device also includes an electrode in electrical contact with the membrane. Such embodiments can, by melting or breaking, provide for the activation and automatic dispensing of a liquid with the lowest possible energy losses due to thermal conduction of the liquids.

Other technical features and advantages are brought about by the techniques of the present invention. Embodiments and aspects of the invention are described in detail herein and are considered part of the claimed subject matter. For a better understanding, reference is made to the detailed description and the drawings.

Figure list

• 1 einen Blockschaltplan zeigt, der ein Beispiel eines Verarbeitungssystems gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung veranschaulicht.
• 2A ein beispielhaftes System gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 2B eine weitere Ansicht des beispielhaften Systems von 2A gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 3A ein beispielhaftes System gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 3B eine weitere Ansicht des beispielhaften Systems von 3A gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 4A ein beispielhaftes System gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 4B eine weitere Ansicht des beispielhaften Systems von 3A gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 5 einen Blockschaltplan der Steuerschaltung gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 6 einen Ablaufplan eines beispielhaften Verfahrens gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.
• 7 einen Ablaufplan eines beispielhaften Verfahrens gemäß einer oder mehreren Ausführungsformen der vorliegenden Erfindung zeigt.

The particularities of the exclusive rights described herein are set out in detail and expressly claimed in the claims at the end of the description. The above and other features and advantages of the embodiments of the invention will become apparent from the following detailed description in conjunction with the accompanying drawings, wherein:

• 1 Figure 12 is a block diagram illustrating an example of a processing system in accordance with one or more embodiments of the present invention.
• 2A Figure 11 shows an exemplary system in accordance with one or more embodiments of the present invention.
• 2 B another view of the exemplary system of FIG 2A according to one or more embodiments of the present invention.
• 3A Figure 11 shows an exemplary system in accordance with one or more embodiments of the present invention.
• 3B another view of the exemplary system of FIG 3A according to one or more embodiments of the present invention.
• 4A Figure 11 shows an exemplary system in accordance with one or more embodiments of the present invention.
• 4B another view of the exemplary system of FIG 3A according to one or more embodiments of the present invention.
• 5 Figure 12 shows a block diagram of the control circuit in accordance with one or more embodiments of the present invention.
• 6th Figure 11 shows a flow diagram of an exemplary method in accordance with one or more embodiments of the present invention.
• 7th Figure 11 shows a flow diagram of an exemplary method in accordance with one or more embodiments of the present invention.

The graphs shown herein are provided for illustrative purposes. There can be many variations on the diagrams or the operations described therein without departing from the spirit of the invention. For example, the actions can be carried out in a different order, or actions can be added, omitted or changed. Furthermore, the term “connected to” and its variants describes that there is a connection between two elements for exchanging data, but no direct connection between the elements without further elements / connections between them. All of these variants are regarded as part of the description.

In the accompanying figures and the following detailed description of the described embodiments, the various elements illustrated in the figures are provided with two- or three-digit reference numbers. With a few exceptions, the leftmost digits correspond to the reference number of the figure in which this element was first illustrated.

DETAILED DESCRIPTION

For the sake of simplicity, conventional techniques relating to semiconductor device and integrated circuit (IC) fabrication may not be described in detail herein. In addition, the various tasks and process steps described herein can be incorporated into a more extensive procedure or a corresponding process that has further steps or functionalities not described in detail herein. In particular, various steps for manufacturing semiconductor devices and ICs based on semiconductors are well known, so that for the sake of simplicity, many conventional steps are only briefly mentioned herein or are completely omitted without illustrating well-known process details.

In reviewing technologies that are more important to aspects of the invention, it is found that digital output devices may be desirable in applications that can automatically benefit from accurate scheduling and / or release of accurate amounts of substance. In drug dispensing applications, for example, digital dispensing units may contain a plurality of containers that are remotely opened according to a precisely defined dispensing and schedule. In some cases, including pharmaceutical applications as well as non-pharmaceutical related applications, digital output devices can be used to provide a means for automatically initiating or terminating a chemical reaction. For example, in applications with microbatteries, the microbattery can be automatically activated remotely by digitally releasing an electrolyte from a container. In another application, an arrangement of biosensors in a rear wall is designed in such a way that they react to specific biomarkers after chemical activation. The surfaces of the biosensors can be cleaned before use. The individual biosensors can be sealed and protected by a membrane, and each biosensor can be located near a container with a liquid chemical substance that activates the surface of the sensor to detect the biomarker of an analyte. After sending an activation signal, both the membrane of the container with the chemical activating substance and the membrane for sealing the biosensor are opened. In some cases, the digital dispensing units can be connected to sensor systems in order to provide an automatic drug dispensing system in a circulatory process.

Their ability to remotely dispense substances from digital dispensing devices makes them potentially applicable in implantable or wearable devices. For example, treatment of certain medical indications may require the administration of materials that are not suitable or optimal for oral administration, or the delivery of materials at a precise dosage or on a schedule. In such applications, drug delivery implants are useful for delivering drugs on a precise schedule with minimal patient or healthcare provider intervention. In addition to implanted systems, digital output devices could provide similar output benefits in portable (e.g., transdermal, transmucosal, etc.) systems as in self-adhesive patch systems.

Using digital output devices in applications where device size is a concern, such as in implantable or portable devices, places demands on system design. Apart from patient and healthcare provider requirements for small units for patient convenience, there may be limitations on the physical dimensions of units that can be implanted in or carried by the patient. Accordingly, the requirements for energy storage and power supply can be significantly reduced by using smaller unit volumes. By minimizing the energy required to release it from a container, the design and performance of the unit can be improved.

Thermal conduction within the unit structure can lead to considerable energy losses in digital output units. For example, high heat conduction can occur in containers with liquids in them.

Conventional digital output devices may include a breakable metal membrane covering a container. In order to release a substance from the container, the membrane can be activated by providing an electrical current which is sufficient to tear or melt the membrane and thereby expose the opening of the container to the environment. However, liquids are good conductors of heat. Before the membrane ruptures or melts, the liquid in the container or cavity that is in contact with the membrane extracts additional energy from the system. However, the energy absorbed from the system can also vaporize the liquid in contact with the membrane. Such evaporation can not only require additional heat, but also potentially degrade or damage thermally sensitive materials in the container.

Some conventional digital output units may contain detachable diaphragms, such as diaphragms attached to the base of the unit via a hinge. After activation by supplying energy to the system, the membrane can partially detach from the structure and as a result, liquid in a container or cavity is released into the environment. For reasons similar to the above, liquids in contact with the sealing rings of such units may require more energy to open the membrane.

Conventional methods of reducing energy losses with respect to liquid containers may include lyophilizing intended container materials to reduce and / or eliminate container liquids. Lyophilization (freeze-drying) is a process in which water is removed from a sample by freezing a designated solution and sublimed from the frozen solution under low pressure, leaving a dried or powdered sample. Lyophilization, however, can not only incur additional costs and additional process steps, it can also be unsuitable for certain compounds and require additional steps to reconstitute before the desired substance is administered to its destination. In order for lyophilization to be inexpensive, large batches may often have to be processed. There remains a need to reduce heat conduction in digital dispensing systems, particularly in systems that contain liquids in the containers.

In the context of an overview of aspects of the invention, one or more embodiments of the invention eliminate the above-described disadvantages according to the prior art by providing a hydrophobic layer on the release membrane of a digital output unit. According to some embodiments of the invention, a container is sealed at an end opposite the membrane and the hydrophobic layer by a second substrate. According to some embodiments of the invention, the second substrate can contain a hydrophilic surface. By means of such embodiments of the invention, the liquid can be drawn towards the hydrophilic surface and away from the membrane.

By means of the aspects of the invention described above, the disadvantages of the prior art are overcome by reducing the conduction of heat in the unit structure by repelling liquid substances from the container or the cavity of the membrane. According to some embodiments of the invention, the hydrophobic layer forms an air cushion between a surface of the liquid container and the membrane, the air cushion providing thermal insulation and improved thermal properties.

1 Figure 3 shows one embodiment of a processing system 100 to practice the teachings set forth herein. According to this embodiment of the invention, the system has 100 one or more processing units (processors) 101a , 101b , 101c etc. (collectively or representatively referred to as the processor (s)). According to one embodiment of the invention, each processor 101 contain a reduced instruction set computer microprocessor (RISC). The processors 101 are through a system bus 113 with a system memory 114 and various other components connected. A read-only memory (ROM) 102 is with the system bus 113 and may contain a basic input / output system (BIOS) that performs certain basic functions of the system 100 controls.

1 also shows an input / output (I / O) adapter 107 and a network adapter 106 that are connected to the system bus 113 are connected. The I / O adapter 107 can be a small computer system interface adapter (SCSI) that transfers data to a hard drive 103 and / or a tape storage drive 105 or any other component. The I / O adapter 107, the hard drive 103 and the tape storage drive 105 are used herein as a mass storage device 104 designated. An operating system 120 to run on the processing system 100 can in the mass storage 104 be saved. Through a network adapter 106 is the bus 113 with an external network 116 connected to it the data processing system 100 Can exchange data with other similar systems. A screen (e.g., a display monitor) 115 is connected to the system bus 113 through a display adapter 112 connected, which may include a graphics adapter to improve the performance of graphics-intensive applications and video control. According to one embodiment of the invention, the adapter 107 , 106 , 112 be connected to one or more I / O buses which are connected to the system bus via an intermediate bus bridge (not shown) 113 are connected. Suitable I / O buses for connecting peripheral units such as hard disk controllers, network adapters and graphics adapters usually contain uniform protocols such as a connection bus for expansion components (PCI). Further input / output units are shown, which are connected via the user interface adapter 108 and the display adapter 112 with the system bus 113 are connected. There is also a keyboard 108 , a mouse 110 and a speaker 111 through the user interface adapter 113 interconnected, which may contain, for example, an I / O superchip for combining multiple unit adapters into a single integrated circuit.

According to exemplary embodiments of the invention, the processing system includes 100 a graphics processing unit 130 . At the graphics processing unit 130 is it a Specialized electronic circuit for editing and changing a memory to speed up the generation of images in an image memory to be displayed on a screen. In general, it is the graphics processing unit 130 very powerful in processing computer graphics and image processing and has a highly parallel structure, which makes it more powerful than general-purpose computers for algorithms in which large blocks of data are processed in parallel.

According to the arrangement in 1 contains the system 100 thus processing capacity in the form of processors 101 , Storage capacity with a system memory 114 and a mass storage device 104 , Input means such as a keyboard 109 and a mouse 110 and output means with a loudspeaker 111 and a screen 115 . According to one embodiment of the invention, an area of system memory is used 114 and mass storage 104 together for storing an operating system such as the AIX operating system ^® by IBM Corporation for controlling the functions of the various in 1 components shown.

Aspects of the present invention will now be described in detail, wherein 2A a hydrophobic dispensing system 200 shows according to embodiments of the invention. The system 200 contains a first substrate 210 , the one in the surface of the substrate 210 formed container 222 contains. The system 200 can be a first layer of sacrifice 212 on top of the first substrate 210 contain. The sacrificial layer 212 may for example contain silicon nitride (SiN) or silicon dioxide (SiO ₂ ). The system 200 may include an electrode layer that is a stack of a plurality of metal layers with a plurality of metal layers 214 , 216 , 218 contains. The system 200 can also be a membrane 220 included that are in contact with one or more of the metal layers 214 , 216 , 218 stands and an opening of the container 220 covered. The membrane 220 may contain a metal thin film, for example a metal thin film with a thickness of about 1 µm. The membrane 220 may also contain a metal that tears or melts after activation, and for example gold, aluminum, indium or a reactive material consisting of a stack of metal layers such as nickel and aluminum or aluminum and palladium. The membrane 220 can also contain electrically insulating dielectric materials such as silicon dioxide (SiO ₂ ), silicon nitride (SiN) or polymer materials. According to some embodiments of the invention, the membrane contains 220 a hydrophobic layer 224 on one of the cavity 222 facing surface. The system 200 can be a second sacrificial layer 226 at the bottom of the substrate 210 contain. The second layer of sacrifice 226 can be the same material as the first sacrificial layer 212 , for example SiN _x or SiO ₂ , or a different material as the first sacrificial layer 212 contain. The system 200 can also be a waterproofing layer 208 and a container seal 206 contain. The waterproofing layer 208 and the container seal 206 may include a low melting point material such as a metal coated polymer layer containing indium (In). The container seal 206 can with a second substrate 209 be connected that has a biocompatible layer 202 Contains that with a metal compatible layer 204 is coated. According to some embodiments of the invention, the container seal provides a permanent and / or irreversible seal for the container.

The waterproofing layer 208 and the seal 206 can open an opening of the container 222 and be such that they enclose the cavity 222 seal and retain a substance within the cavity. To illustrate, there is only one cavity 222 shown, however, it should be understood that the substrate 210 can be formed as an array of cavities containing, for example, hundreds of cavities that serve as containers for storing the same or a combination of different substances to be dispensed.

The number of metal layers can vary depending on the desired application of the system. For example, a system with a greater number of container types or with a relatively complex release schedule may contain a greater number of metal layers than a system with fewer container types or with a simpler release schedule. The metal layers 214 , 216 , 218 may contain metallic materials such as copper, gold, platinum or titanium and take the form of metal layers or structured layers containing metallic electrode elements, including copper, gold, platinum or titanium, formed in one or more layers of silicon dioxide. According to some embodiments of the invention, electrodes are in electrical contact with the membrane in order to supply current, for example for heating the membrane or a part of the membrane. The stack of several metal layers can be such that part of the membrane 220 is heated locally by it.

The cavity 222 may have a diameter suitable for containing a liquid in an amount sufficient for the desired application, for example from about 1 to about 100 nanoliters (nl) or about 10 to about 50 nl of liquid. The cavity 222 For example, it may have a diameter in the range of about 100 micrometers to about 1 millimeter (mm) and a depth of about 100 to about 500 micrometers.

The biocompatible layer 202 contains a biocompatible substrate, for example a substrate that contains polydimethylsiloxane (PDMS), silicon, glass, polyimide such as KAPTON ^® or a biocompatible cement. The metal compatible layer 204 may contain a material that interacts with the seal 206 connected is. According to some embodiments of the invention, the metal compatible layer includes 204 Gold.

The hydrophobic layer 224 can be deposited, grown on or formed on the structure, for example by plasma deposition, surface treatment, coating or nano-coating, electroplating. The hydrophobic layer 224 may contain materials with a hydrophobicity sufficient to repel a desired aqueous material in the container. The hydrophobic layer can, for example, be fluorocarbons such as Teflon, Teflon-like materials or other plasma-coated hydrophobic fluorinated thin films; microstructured polymers such as PDMS or SU-8; Nanocoatings such as coatings containing silicon dioxide particles, polytetrafluoroethylene (PTFE) or aluminum oxide particles; electrodeposited metal layers such as porous gold layers; Oxides and oxide composite materials such as magnesium oxide-polystyrene (MnO ₂ / PS) nanocomposite material or zinc oxide-polystyrene (ZnO / PS) nanocomposite material, precipitated calcium carbonate, carbon nanotubes; or contain structured layers such as, for example, layers with a columnar and / or groove structure. According to some embodiments of the invention, the membrane and at least a part of the cavity, like the cavity walls adjacent to the membrane, have the hydrophobic layer 224 lined. The hydrophobic layer can have a thickness from about 0.5 nanometers (nm) to about 1 micrometer. According to some embodiments of the invention, at least a part of the membrane contains an electrically insulating layer.

2 B shows the exemplary hydrophobic dispensing system 200 of 2A after activation according to some embodiments of the invention. After activating the membrane 220 and the hydrophobic layer 224 removed from the unit, for example by tearing or melting the membrane after being excited by an electric current, so that the cavity 222 is accessible from the surrounding area.

Hydrophobic dispensing systems according to embodiments of the invention can be fabricated using common materials and semiconductor manufacturing processes including, for example, microelectromechanical (MEMS) technology, back-end-of-line (BEOL) technology, photolithography, wafer bonding, wafer thinning, and the like Wafer transfer processes. According to some embodiments of the invention, materials that are biocompatible or can be made biocompatible by coating with suitable biocompatible substances are used to construct dispensing systems.

For example, the substrate can 210 using any standard semiconductor material such as silicon or formed by glass, ceramic, etc., materials that are, for example, micromachined or using standard etching processes (e.g. anisotropic wet chemical etching or deep ionic etching (DRIE)) and wafer thinning processes can be etched. The substrate 210 can be formed using a biocompatible material such as silicon that is impermeable to the liquid contained in the etched cavities. The dimensions and shape of the cavity 222 and the number of in the substrate 210 cavities formed depend on the particular application. According to one embodiment of the invention, it is the cavities 222 around circular cavities formed in a silicon substrate using an RIE deep etch process. In accordance with other embodiments of the invention, the cavities may be in the form of quadrilateral truncated cones formed by anisotropic wet etching of (100) -oriented silicon.

According to some embodiments of the invention, a cavity 222 in a substrate prior to closing the cavity 222 filled with liquid. For example, a cavity 222 before connecting the container seal 206 with a second substrate 209 be filled with a liquid. According to such embodiments of the invention, this sealing process is characterized in that the filling process into the cavity 222 the substance entering is not negatively influenced or otherwise damaged.

According to some embodiments of the invention, the hydrophobic dosing system can contain sensors. Sensors can include any sensor device useful in a miniaturized or automated dispensing system. Possible sensors are, for example, pH sensors, ion sensors, pulse sensors, blood pressure sensors, flow sensors, humidity sensors, action potential sensors, potential sensors for local fields, chemical sensors such as nucleic acid sensors, protein sensors, exosome sensors, glucose sensors or special neurotransmitter sensors, optical sensors or acoustic sensors.

3A shows the exemplary hydrophobic dispensing system 200 of 23A at a exemplary process step of filling the unit with a liquid. The system 200 contains a substrate 210 , the one in the surface of the substrate 210 formed cavity 222 contains. The system 200 can be a first layer of sacrifice 212 on top of the substrate 210 contain. The sacrificial layer 212 may for example contain silicon nitride (SiN) or silicon dioxide (SiO ₂ ). The system 200 may include a stack of multiple metal layers that includes a plurality of metal layers 214 , 216 , 218 contains. The system 200 can also be a membrane 220 included that are in contact with one or more of the metal layers 214 , 216 , 218 stands and the cavity 220 covered. The membrane 220 may include a thin metal layer, for example a metal layer approximately 1 micrometer thick. The membrane 220 contains a metal that can be torn, melted, or partially melted when activated. Activating the system to release the contents of a container can consist of a strong current flow through the membrane 220 is provided, for example by means of one or more electrodes in contact with the membrane. The membrane 220 may for example contain aluminum, gold or a reactive material such as a layer structure of aluminum and palladium. A surface of the membrane in the cavity 220 is with a hydrophobic layer 224 lined. One drop of a solution 230 can be filled into the cavity. 3A shows that the solution 230 through the hydrophobic layer 224 can be repelled so that contact with the membrane 220 and the hydrophobic layer 224 is reduced to a minimum, for example by forming a bead.

3B shows the exemplary hydrophobic dispensing system 200 of 3A after sealing the container. The container cavity 222 can by means of a second substrate 209 be sealed. According to some embodiments of the invention, the second substrate can 209 a hydrophilic surface 232 contain. With a hydrophilic surface 232 for example the liquid in the container 230 attracted and from the membrane 220 and the hydrophobic layer 224 be pulled further away. The hydrophilic surface 232 may contain any surface with a biocompatible material including, for example, materials commonly used in semiconductor devices such as silicon (Si), SiO ₂ , SiN _x or other oxides.

4A shows a hydrophobic dispensing system 400 according to another embodiment of the invention. The system 400 contains a substrate 404 , in which one or more cavities can be formed. The system 400 contains a hinged membrane 402 that have a pivoting structure 412 connected is. The pivotable structure can contain a material with a low melting point, for example a polymer layer coated with an indium-containing metal. The membrane and optionally also the hinge or the suspension 412 can inside the container with a hydrophobic layer 224 be lined. According to some embodiments of the invention, on the substrate 40 a plurality of layers can be deposited or formed, for example oxide layers 408 and nitride layers 406 . According to some embodiments of the invention, the system includes 400 a control circuit. According to some embodiments of the invention, the system includes 400 a metal layer 410 that are in contact with the pivoting structure 412 stands. The system can also have electrode elements 420 contain.

4A shows that a liquid 230 filled in the container and with the membrane 402 can be sealed. Through the hydrophobic layer 224 can the liquid in the container 230 be rejected in such a way that the liquid does not come into contact with the membrane. The hydrophobic layer allows an insulating air cushion between the surface of the liquid and the membrane 402 are formed.

4B shows the exemplary hydrophobic dispensing system 400 of 4B after activation according to some embodiments of the invention. After activating the membrane 402 and at least part of the hydrophobic layer 224 partially separated from the structure, for example by means of MEMS technology, so that the container is opened to the local environment and substances can be released within the container. According to some embodiments of the invention, for example, after a part of a seal has melted as a result of local heating by a connected electrode, a hinge can be opened. According to such embodiments of the invention, the membrane 402 be opened so that substances within the container can be released quickly and completely without completely separating the membrane from the dispensing unit. According to some embodiments of the invention, the membrane is standing 402 prior to activation under mechanical tension, and for example the tension can be released by activation in order to enable the membrane to be opened away from the cavity of the container according to the curvature.

In the system of 4A and 4B For example, a melt temperature of about 157 ° C may be required to open the container for a membrane measuring about 100 microns by 100 microns and about 1 micron thick and with a seal made of indium, which corresponds to an amount of energy of about 20 Microjoules (µJ).

Structures according to the 4A and 4B can be fabricated using common semiconductor fabrication techniques including, for example, damascene processes and standard lithographic techniques used to fabricate CMOS multilayer structures.

5 Figure 3 is a block diagram of a control circuit that can be configured to control the release of contents from bins of a microchip dispenser according to an embodiment of the invention. 5 shows one with a power source 514 connected tax system 500 . The tax system 500 can use a microprocessor 508 , a memory 504 like a programmable ROM, one or more sensors 506 , a wireless transmitter / receiver 502 , a demultiplexer circuit 510 and an output assembly 512 contain. Various components of the tax system 500 contain integrated circuits that are formed as an integral part of an output unit that contains a hydrophobic layer. In 5 can the output arrangement 512 for example, as discussed above, include releasable membrane structures and containers. The tax system 500 can be designed using standard circuit design techniques and fabricated using standard silicon-based integrated circuit techniques.

The microprocessor 508 can control signals for the demultiplexer circuit 510 produce to selectively one or more diaphragms of the output assembly 512 to activate. According to some embodiments of the invention, the microprocessor 508 Generate control signals for activating the release of substances according to a programmed schedule stored in the programmable ROM. According to another embodiment of the invention, the microprocessor 508 Generate control signals for activating the release of substances in accordance with control signals received from one or more sensors 506 which automatically detect when a substance should be released according to the local circumstances. For example, a dispensing structure for pharmaceuticals can determine when doses of a particular drug or medicine should be administered at least in part based on the analysis of a biosensor input, for example a local pH value or a local ionic composition, and activate one or more membranes in order to at least partially To release a pharmaceutically active ingredient from one or more containers based on the proven conditions. According to yet another embodiment of the invention, the microprocessor 508 Generate control signals for activating the release of active substances in accordance with control signals issued based at least in part on remote control commands from a wireless receiver, the remote control commands being from a healthcare provider or a person with an implantable or wearable substance dispenser.

According to some embodiments of the invention, the power source can 514 can be implemented as an internal power source such as a biocompatible thin-film battery that is integrated into the microchip output unit for substances. In such embodiments of the invention, the battery capacity is limited by the battery size, the material and the requirements for the packaging, so that the energy requirement for release from the substrate is preferably reduced to a minimum value. In other embodiments of the invention, the energy supply can be ensured by a wireless power supply system, in which the energy is supplied from an external power source, for example by near field communication (NFC), to the control system 514 is transmitted.

6th Figure 3 shows a flow diagram of an exemplary method 600 for dispensing liquid according to one or more embodiments of the present invention. The method includes, for example, forming a hydrophobic liner on a release membrane in a container of the dispensing structure in blocks 602 . The procedure 600 also includes providing a liquid in the container in block 604 . The procedure 600 also includes sealing the container with a hydrophilic layer in block 606 . The procedure 600 also includes providing electrical power to the release membrane to dispense the liquid in block 608 .

7th Figure 3 shows a flow diagram of an exemplary method 700 for dispensing liquids according to one or more embodiments of the present invention. The procedure 700 includes, for example, receiving a signal relating to an environmental condition from a sensor according to block 10 702 . Alternatively, according to some (in 7th Embodiments of the invention (not illustrated) include receiving a signal from an external unit or receiving a signal from a stored schedule. The procedure 700 also includes supplying an electric current according to block 704 to a release membrane coated with a hydrophobic liner covering a container of the dispensing structure. The procedure 700 also includes rupturing the membrane by means of the electrical current according to block 706 .

In the present context, a “liquid” is to be understood as a liquid, water-containing material. As a liquid in Embodiments of the invention can be any liquid that is suitable for dispensing from a miniaturized dispensing unit. Examples of liquids are, without being limited to them, pharmaceutical solutions and preparations, nutrient solutions and preparations, functional food solutions and preparations, catalysts, solvents, reagents, active substance carrier substrates, diluents, preservatives and the like. According to some embodiments of the invention, a container contains one or more pharmaceutically active substances. According to some embodiments of the invention, the container contains an electrolyte, for example a micro battery electrolyte. According to some embodiments of the invention, digital output systems are connected to sensor systems to provide an automatically controlled output system.

In accordance with some embodiments of the invention, fluid dispensing units are incorporated into implantable or portable drug delivery systems. For example, liquid dispensing units can be included in systems whose purpose is the treatment and / or control of diabetes, pain, addictive behavior, contraception, neurological or psychological disorders.

Embodiments of the invention can provide improved liquid dispensing units by using less energy to dispense liquids in a miniaturized unit. A hydrophobic layer adjacent to the membrane can repel liquids from the membrane in the container and thereby release materials from the structure that require less energy.

Some embodiments of the invention provide improved liquid dispensing units by reducing the risk of destruction or deterioration and / or by improving the cohesion of the liquids in the container. A hydrophobic layer adjacent to the membrane repels liquids from the membrane in the container and reduces the risk of the liquids being destroyed, which would be the case when activated by passing an electric current through the membrane.

Herein, various embodiments of the present invention will be described with reference to the accompanying drawings. Alternative embodiments can be devised without departing from the scope of this invention. While various connections and positional relationships (e.g., above, below, adjacent, etc.) between elements are set forth in the following description and in the drawings, those skilled in the art will understand that many of the positional relationships described herein are orientational as long as the functionality described is retained despite the changed orientation. These connections and / or positional relationships can be direct or indirect unless otherwise indicated, and the present invention is not intended to be a limitation in these relationships. Accordingly, a connection of units can be either a direct connection or an indirect connection, and a positional relationship between units can be a direct or an indirect positional relationship. According to an example of an indirect positional relationship, terms in the present description such as forming a layer “A” above a layer “B” refer to cases in which there are one or more intermediate layers between the layer “A” and the layer “B”, as long as the relevant properties and functionalities of layer “A” and layer “B” are not significantly changed by the intermediate layer (s).

The following definitions and abbreviations are used to aid understanding of the claims and description. The terms "has", "having", "contains", "containing", "has", "having", "contains" or "containing" or any other variant thereof, as used herein, are intended to denote non-exclusive inclusion. For example, a composition, mixture, process, method, article, or device that includes a list of items is not necessarily limited to those items alone, but may include other items not specifically listed or not Composition, mixture, such a process, method, object or device are not associated with it from the outset.

In addition, the term “exemplary” used here is to be understood as meaning “serving as an example, individual case or illustration”. Any embodiment or construction described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments or constructions. The terms “at least one” or “one or more” are intended to include any integer greater than or equal to one, ie one, two, three, four, etc. The term “a plurality” is intended to include any integer greater than or equal to two, ie two, three, four, five, etc. The term “connection” can include an indirect “connection” or a direct “connection”.

References in the description to “a single embodiment,” “an embodiment,” “an exemplary embodiment,” etc. indicate that the described embodiment may include a particular feature, structure, or characteristic, but that not every embodiment may include the particular feature, structure, or characteristic. In addition, such expressions do not necessarily relate to one and the same embodiment. Furthermore, when a particular feature, structure or property is described in connection with an embodiment, it is assumed that the person skilled in the art is clear that such a feature, structure or property is also affected thereby in connection with other embodiments, too if this is not expressly described.

In the context of the following description, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom” and their derivatives refer to the structures and processes described shown in the figures. The terms “overlying”, “above”, “on top”, “positioned on” or “positioned above” mean that a first element such as a first structure lies on a second element such as a second structure, with intervening elements such as an interface structure lie between the first element and the second element. The term “direct contact” means that a first element such as a first structure and a second element such as a second structure are connected to one another at the interface between the two elements without intervening conductive, insulating or semiconductor layers.

The term “selective with respect to” such as “a first element selective with respect to a second element” means that the first element can be etched and the second element can serve as an etch stop.

The terms “approximately”, “substantially”, “approximately” and their variants are intended to include an error value associated with the measurement of a certain quantity based on the equipment available at the time of filing the application. For example, the term “approximately” can include a range of ± 8% or 5%, or 2% of a certain value.

It was noted above that, for the sake of simplicity, conventional techniques relating to the manufacture of semiconductor devices and integrated circuits (IC) may not be described in detail herein. However, as background knowledge, what follows is a general description of the processes for fabricating semiconductor devices that may be used to practice one or more embodiments of the present invention. While specific manufacturing steps for implementing one or more embodiments of the present invention may be known from case to case, the described combination of operations and / or resulting structures of the present invention is unique. Thus, the unique combination of the operations described in connection with fabricating a semiconductor device in accordance with the present invention utilizes a variety of distinct known physical and chemical processes to which a semiconductor (e.g., silicon) is subjected, some of which are described in the paragraphs immediately below.

In general, the various processes used to form a microchip for an IC are grouped into four general categories, ie, film deposition, ablation / etching, semiconductor doping, and patterning / lithography. Deposition is any process in which a material is transferred to the wafer by growth, coating or in some other way. Technologies available include physical vapor deposition (PVD), chemical vapor deposition (CVD), electrochemical deposition (ECD), molecular beam epitaxy (MBE), and more recently, atomic layer deposition (ALD), and others. Ablation / etching is any process that removes material from the wafer. Examples include etching processes (wet or dry), chemical mechanical polishing (CMP), and the like. Semiconductor doping is changing the electrical properties by doping, for example the source and drain electrodes of the transistors, which is generally done by diffusion and / or by implantation. These doping processes are followed by tempering in a tempering furnace or rapid thermal annealing (RTA). Annealing is used to activate the implanted dopants. Layers of both conductors (e.g., polysilicon, aluminum, copper, etc.) and insulators (e.g., various forms of silicon dioxide, silicon nitride, etc.) are used to connect and isolate the transistors and their components. By selectively doping different areas of the semiconductor substrate, it is possible to change the conductivity of the substrate by applying a voltage. By creating structures from these various components, millions of transistors can be built and interconnected to form the complex circuitry of a modern microelectronic device. Semiconductor lithography is the formation of three-dimensional relief images or patterns on the semiconductor substrate in order to then transfer the pattern onto the substrate. In semiconductor lithography, the patterns are formed by a photosensitive polymer called photoresist. To create the complex structures that make up a transistor and the many wires that connect the millions of transistors in a circuit, the lithographic steps for transferring etching patterns are repeated many times. Each pattern transferred to the wafer is aligned with the previously formed pattern and the conductors, insulators and selectively doped areas are gradually stacked on top of one another to form the final assembly.

The computer readable storage medium can be any physical entity that can retain and store instructions for use by an instruction execution system. The computer-readable storage medium can be, for example, an electronic storage unit, a magnetic storage unit, an optical storage unit, an electromagnetic storage unit, a semiconductor storage unit, or any suitable combination thereof, without being limited thereto. A non-exhaustive list of more specific examples of computer readable storage media include the following: a portable computer disk, hard drive, random access memory (RAM), read only memory (ROM), erasable programmable read only memory (EPROM or flash memory), a static random access memory (SRAM), a portable compact disk read-only memory (CD-ROM), a DVD (digital versatile disc), a memory stick, a floppy disk, a mechanically encoded unit such as for example punch cards or raised structures in a groove on which instructions are stored, and any suitable combination thereof. A computer readable storage medium, when used herein, is not to be construed as being volatile signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission medium (e.g., pulses of light passing through a fiber optic cable ) or electrical signals transmitted through a wire.

Computer-readable program instructions described herein can be transferred from a computer-readable storage medium to respective data processing / processing units or via a network such as the Internet, a local area network, a wide area network and / or a wireless network to an external computer or a external storage device. The network can comprise copper transmission cables, fiber optic transmission conductors, wireless transmission, routing computers, firewalls, switching units, gateway computers and / or edge servers. A network adapter card or network interface in each data processing unit receives computer-readable program instructions from the network and forwards the computer-readable program instructions for storage in a computer-readable storage medium within the corresponding data processing / processing unit.

Computer-readable program instructions for performing operations of the present invention can be assembler instructions, instruction set architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, condition-setting data, or either source code or object code that are written in any combination of one or more programming languages, including object-oriented programming languages such as Smalltalk, C ++ or similar, as well as conventional procedural programming languages such as the "C" programming language or similar programming languages. The computer-readable program instructions can run entirely on the user's computer, partially on the user's computer, as a stand-alone software package, partially on the user's computer, and partially on a remote computer, or entirely on the remote computer or server. In the latter case, the remote computer can be connected to the user's computer through any type of network, including a local area network (LAN) or wide area network (WAN), or the connection can be made to an external computer (for example via the Internet using an Internet Service Provider). In some embodiments, electronic circuits, including, for example, programmable logic circuits, field programmable gate arrays (FPGA), or programmable logic arrays (PLA), can execute the computer-readable program instructions by transferring state information from the computer-readable program instructions utilize human readable program instructions to personalize the electronic circuitry to carry out aspects of the present invention.

Aspects of the present invention are described herein with reference to flow charts and / or block diagrams or diagrams of methods, devices (systems) and computer program products according to embodiments of the invention. It should be noted that each block of the flowcharts and / or the block diagrams or graphs as well as combinations of blocks in the flowcharts and / or the block diagrams or graphs can be executed by means of program instructions that can be read by a computer.

These computer-readable program instructions can be provided to a processor of a general-purpose computer, a special purpose computer or other programmable data processing device in order to generate a machine, so that the instructions executed via the processor of the computer or the other programmable data processing device are a means for implementing the in Generate functions / steps specified for the block or blocks of the flowcharts and / or block diagrams. These computer-readable program instructions can also be stored on a computer-readable storage medium which can control a computer, a programmable data processing device and / or other units to function in a certain way, so that the computer-readable storage medium , on which instructions are stored, has a manufacturing product which contains instructions for implementing aspects of the function / step specified in the block or blocks of the flowchart and / or the block diagram.

The computer readable program instructions can also be loaded onto a computer, other programmable data processing device, or other device to cause a series of process steps to be performed on the computer or other programmable device or other device, such as one on a computer to generate the executed process, so that the instructions executed on the computer, another programmable device or another unit implement the functions / steps specified in the block or blocks of the flowcharts and / or the block diagrams.

The flowcharts and the block diagrams or diagrams in the figures illustrate the architecture, functionality and operation of possible implementations of systems, methods and computer program products in accordance with various embodiments of the present invention. In this context, each block in the flowcharts or block diagrams can represent a module, a segment or a part of instructions that comprise one or more executable instructions for carrying out the particular logical function (s). In some alternative implementations, the functions noted in the block may take place out of the order shown in the figures. For example, two blocks shown in sequence may in fact be executed essentially simultaneously, or the blocks may sometimes be executed in reverse order depending on the functionality involved. It should also be noted that each block of the block diagrams and / or the flowcharts and combinations of blocks in the block diagrams and / or the flowcharts can be implemented by special hardware-based systems that carry out the specified functions or steps, or combinations of special Follow hardware and computer instructions.

The descriptions of the various embodiments of the present invention have been presented for purposes of illustration, but are not intended to be exhaustive or restrictive of the embodiments described. Many modifications and variants will be apparent to those skilled in the art without departing from the scope and spirit of the embodiments described. The terms used herein were chosen in order to explain the basic ideas of the embodiments of the invention, the practical application or the technical improvement over commercially available technologies as well as possible, or to facilitate the understanding of the embodiments described herein for other persons skilled in the art.

Claims (8)

A liquid dispensing device (200) comprising: a first substrate (210) having a container (222) formed in the first substrate; a liquid (230) received in the container (222); a membrane (220) disposed on the surface of the first substrate and covering an opening of the container (222); a second substrate (209) adhered to the first substrate (210), the second substrate including a container seal (206); a hydrophobic layer (224) disposed on an inner surface of the membrane (220), the hydrophobic layer (224) forming an air cushion between a surface of the liquid and the membrane (220); Electrodes in electrical contact with the membrane (220); and a hydrophilic layer (232) disposed on a surface of the container (222) opposite the membrane (220). Device according to Claim 1 wherein at least a part of the membrane (220) comprises a metal layer (214; 216; 218). Device according to Claim 1 wherein at least a part of the membrane (220) has an electrically insulating layer. Device according to Claim 1 wherein the container seal (206) comprises indium. Device according to Claim 1 wherein the hydrophobic layer (224) comprises a fluorocarbon layer. Device according to Claim 1 further comprising a sensor (506). Device according to Claim 1 wherein the hydrophobic layer (224) comprises a porous electrodeposited metal layer. Device according to Claim 1 wherein the hydrophobic layer (224) has a thickness of about 0.5 nanometers (nm) to about 1 micrometer. 9. Device according to Claim 1 wherein the liquid (230) comprises a pharmaceutically active agent. 10. Device according to Claim 1 wherein the liquid (230) comprises a micro battery electrolyte. 11. Device according to Claim 1 wherein part of the cavity (222) is lined by the hydrophobic layer (224).

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